Investigation of microsphere-mediated cellular delivery by chemical, microscopic and gene expression analysis.

Abstract:

:Amino functionalized cross-linked polystyrene microspheres of well defined sizes (0.2-2 mum) have been prepared and shown to be efficient and controllable delivery devices, capable of transporting anything from small dye molecules to bulky proteins into cells. However, the specific mechanism of cellular entry is largely unknown and widely variant from study to study. As such, chemical, biological and microscopic methods are used to elucidate the mechanism of cellular uptake for polystyrene microspheres of 0.2, 0.5 and 2 mum in mouse melanoma cells. Uptake is found to be wholly unreliant upon energetic processes, while lysosomal and endosomal tracking agents failed to show co-localisation with lysosomes/endosomes, suggesting a non-endocytic uptake pathway. To further explore the consequences of microsphere uptake, gene expression profiling is used to determine if there is a transcriptional response to "beadfection" in both murine and human cells. None of the common transcriptional responses to enhanced endocytosis are observed in beadfected cells, further supporting a non-endocytic uptake mechanism. Furthermore, the microspheres are noted to have a limited interaction with cells at a transcriptional level, supporting them as a non-toxic delivery vehicle.

journal_name

Mol Biosyst

journal_title

Molecular bioSystems

authors

Alexander LM,Pernagallo S,Livigni A,Sánchez-Martín RM,Brickman JM,Bradley M

doi

10.1039/b914428e

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

399-409

issue

2

eissn

1742-206X

issn

1742-2051

journal_volume

6

pub_type

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